Iron deficiency in first-time and repeat blood donors presents an ongoing challenge in transfusion medicine. Iron is an essential element that is lost with each blood donation. In order for a donor to compensate for the iron lost in donating blood, iron is mobilized from the body?s iron stores and absorption of iron from the diet is increased. However, this balance is often difficult to maintain in premenopausal women and in frequent, regular blood donors. Deficiency in iron results in reduced hemoglobin values, reduced iron stores, and eventually iron deficiency anemia, if not treated. Iron deficiency presents a problem in blood centers since the minimum allowable hemoglobin for blood donation established by the FDA is 12.5 g/dL. In the Department of Transfusion Medicine at the NIH, 14.6% of donors presenting for whole blood donation and 7.7% of donors presenting for platelet apheresis donation are deferred on at least one occasion per year due to low hemoglobin values. Overall, 7.9% of visits for whole blood donation and 2.1% of visits for apheresis platelet donation result in donor deferral due to low hemoglobin. Deferral for low screening hemoglobin values negatively impacts donor recruitment, donor retention, and the ability to meet growing demands on the blood supply. [unreadable] [unreadable] Although the challenge of iron depletion in the blood donor population has been known for decades, little has been undertaken to resolve this issue. Several authors have reported data from successful short term projects demonstrating the safety and efficacy of iron replacement in donors, but larger long term studies have not been reported. The objectives of this protocol are to: (1) quantitate the prevalence of iron depletion and iron deficiency anemia in both first-time and repeat healthy individuals who present for blood donation; (2) study the effects of long-term blood donation on donors? hemoglobin levels and iron stores; (3) evaluate the safety, practicality, and efficacy of distributing oral replacement iron to blood donors; (4) determine the effect of oral iron replacement therapy on the donor pool by monitoring deferral rates for low hemoglobin before and after the initiation of an iron replacement program. The goal of these objectives is to treat and prevent iron deficiency in prospective and regular blood donors, thereby expanding the eligible donor pool and leading to increased donor satisfaction and retention by decreasing deferral rates due to low hemoglobin. [unreadable] [unreadable] Each donation of whole blood results in an iron loss of about 240 mg in men and 220 mg in women. It is known that about 6-8% of the iron given as an oral ferrous salt is absorbed daily by iron-depleted donors. Therefore, since approximately 220-240 mg of iron is lost with each blood donation, administration of 65 mg of elemental iron daily for 60 days would completely replace the iron lost through a whole blood unit donation (6% of 65 mg is 3.9 mg daily, or 234 mg over 60 days). Oral iron replacement in this study will consist of ferrous sulfate, one 325 mg tablet daily, containing 65 mg of elemental iron, to be given for 60 days at the time of a deferral for low hemoglobin. This regimen will also be repeated at the time of every future blood donation, to prevent recurrence of iron deficiency. Compliance with and tolerance to oral iron therapy and resolution of symptoms of iron deficiency will be monitored. Donors with gastrointestinal intolerance to ferrous sulfate will be offered ferrous gluconate. In this manner, each time such a donor gives a unit of blood at the NIH Department of Transfusion Medicine, they will receive a 60-pack of an oral iron tablet to replace the iron lost through the donation. These formulations of oral iron are available as over-the-counter medications, but will be provided free of charge to donors in this protocol, through the NIH pharmacy.